HDAC8 p.Ile172=
c.516T>A · rs61752447 · VCV712765
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.905%, sas)
Conditions
1
Cornelia de Lange syndrome 5
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.1 | GERP 0.21, phastCons 1 |
| Overall | ||
| CADD | 9.032 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.905%
South Asian · 512/56,593 alleles
Filtering AF
0.84%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.814%
Overall
0.0453%
546/1,206,087 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.905% | 111 |
| Remaining individualsnot grpmax-eligible | 0.0569% | 1,758 |
| African / African-American | 0.0035% | 28,552 |
| European (non-Finnish) | 0.00056% | 178,423 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- HDAC8
- Protein
- p.Ile172=
- Coding
- c.516T>A
- MANE Select
- NM_018486
- dbSNP
- rs61752447
- Type
- single nucleotide variant
- Location
- chrX:72495190 (GRCh38)
- Structure
- AlphaFold pLDDT 95.45 · 53 PDB
- Residue 172
- the 'histone deacetylase' region; a β-strand
Similar variants
- HDAC8 c.165-2A>G Pathogenic ★★ same condition
- HDAC8 c.738-1G>A Pathogenic ★★ same condition
- HDAC8 c.738-2A>G Pathogenic/Likely pathogenic ★★ same condition
- HDAC8 p.Arg164Ter Pathogenic ★★ same condition
- HDAC8 p.Arg313Ter Pathogenic ★★ same condition
- HDAC8 p.Arg37Gln Pathogenic/Likely pathogenic ★★ same condition
- HDAC8 p.Asn156Ser Pathogenic ★★ same condition
- HDAC8 p.Gln263Ter Pathogenic ★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/hdac8-p-ile172 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown